This proposal is based on our finding that 100% effective contraception can be obtained in female guinea pigs immunized with the sperm protein PH-20. Using the guinea pig model, we can now critically test hypotheses about the long-term feasibility, mechanism of action and safety of effective immuno-contraception. the first four aims are; I. Test if 100% effective contraception in female guinea pigs can be induced for one year (or longer) by systemic hyper-immunization with PH- 20 or alternate routes of PH-20 administration. II. Test the hypothesis that frequent mating will boost the immune response and prolong the contraceptive state in female guinea pigs immunized with PH-20. III. Determine the mechanism of infertility in PH-20 immunized female guinea pigs and study the levels of antibody in the reproductive tract. Test for abnormalities in young born to immunized females who regain fertility. IV. Determine if recombinant PH-20. produced from the cloned PH-20 gene, is as effective a contraceptive immunogen as PH-20 purified from sperm. To develop an anti-sperm contraceptive vaccine for use by women. the human sperm surface protein(s) to be used as antigen must be identified and the corresponding gene(s) cloned. To pursue this direction, the last two aims of this proposal are: V. Test the hypothesis that a structural and/or functional analog of PH- 20 is present on human sperm. VI. Identify and clone the genes for human sperm surface antigens, structurally unrelated to PH-20, which have properties appropriate for a contraceptive immunogen.